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通过分析微阵列数据集,确定与肺腺癌中奥西默提尼布耐药性相关的circRNA-miRNA-mRNA网络

Fen Liu¹, Xiyan Wang¹, Wenjun Tian²

¹Department of Respiratory, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Institute of Anesthesia and Respiratory Critical Medicine, Jinan, 250014, China.

Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer

|June 10, 2025

概括

这项研究确定了一个circRNA-miRNA-mRNA网络,特别是hsa_circ_0078465/miR-183-5p/NRAS轴,它促进肺腺癌 (LUAD) 中的奥西默提尼布耐药性. 这一发现为克服抗药性提供了潜在的治疗点.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

肺腺癌 (LUAD) 经常会对针对性疗法奥西默蒂尼布产生耐药性.
了解这种耐药性背后的分子机制对于改善患者的治疗结果至关重要.

研究的目的:

在LUAD中选与 osimertinib 耐药性相关的循环RNA (circRNAs).
构建一个circRNA-miRNA-mRNA竞争的内源RNA (ceRNA) 网络.
为了确定奥西默提尼布耐药性的关键分子参与者.

主要方法:

使用DESeq2对GEO数据库数据进行差异表达分析,以识别circRNAs.
不同表达的miRNA与circRNA点和EGFR相关基因的交叉.
在细胞模型中验证已识别的hsa_circ_0078465/miR-183-5p/NRAS轴.

主要成果:

一个网络将与 osimertinib 耐药性相关的 circRNA 与六种差异表达的 miRNA 和 35 种与 EGFR 相关的 mRNA 联系起来.
NRAS被确定为这个网络中的一个枢纽基因.
验证了hsa_circ_0078465/miR-183-5p/NRAS轴,并表明它可以促进对异星丁尼抗性LUAD细胞的增殖和迁移.

结论:

这项研究提出了一种新的circRNA-miRNA-mRNA网络,特别是hsa_circ_0078465/miR-183-5p/NRAS轴,涉及到LUAD中 osimertinib 耐药性.
这个轴在调节细胞运动和增殖方面发挥着作用.
这些发现提供了潜在的治疗点,以克服LUAD中 osimertinib 耐药性.

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